Perlecan is a large heparan sulfate proteoglycan that is typically found in basal lamina of adult and embryonic tissues. Recent studies have demonstrated that perlecan accumulates impressively during cartilage development and is maintained as the major heparan sulfate proteoglycan of adult cartilage. In vertebrates, perlecan mutations result in skeletal defects. Moreover, in vitro studies indicate that perlecan can stimulate early stages of cartilage differentiation and cooperate with chondrogenic growth factors to promote this process. This short article will summarize these results and propose a model for perlecan function that incorporates these genetic and cell biological findings. Copyright 2004 S. Karger AG, Basel